Megakaryocytes transfer mitochondria to bone marrow mesenchymal stromal cells to lower platelet activation

Area of Science:

• Hematology
• Cell Biology
• Mesenchymal Stem Cell Biology

Background:

• Newly produced platelets are typically in a low activation state, but the role of megakaryocytes in this process is not fully understood.
• Mesenchymal stem cells (MSCs) are known to promote platelet production and reduce platelet activation.

Purpose of the Study:

• To investigate the role of megakaryocyte-mesenchymal stem cell interactions in regulating platelet activation.
• To explore the impact of sickle cell disease (SCD) microenvironment on these interactions and platelet function.

Main Methods:

• Investigated mitochondrial transfer between megakaryocytes and MSCs in healthy and SCD models.
• Analyzed the role of connexin 43 (Cx43) gap junctions in mediating mitochondrial transfer.
• Assessed platelet energetic state, glycolysis, and LYN activation in relation to MSC interactions and heme exposure.

Main Results:

• Healthy megakaryocytes transfer mitochondria to MSCs via Cx43, resulting in low-energy platelets with resting characteristics.
• In SCD, heme exposure reduces MSCs' Cx43 expression and mitochondrial uptake, leading to impaired LYN activation and heightened platelet activation.
• Platelets in SCD exhibit an elevated energetic state with increased glycolysis.

Conclusions:

• Hemolysis in the SCD microenvironment disrupts megakaryocyte-MSC communication, promoting platelet hyperactivation.
• These findings highlight the role of hemolysis-induced environmental changes in SCD pathophysiology.
• The study suggests potential therapeutic targets for mitigating thrombosis-related complications in SCD and other hemolytic conditions.